1. Field of the Invention
This invention relates to new anthracycline antibiotics, to their production and recovery, and to their therapeutic use.
2. Description of the Prior Art
A number of anthracycline glycosides have been described in the literature. Among them, daunomycin and adriamycin are particularly being watched with keen interest in the field of cancer chemotherapy and have already been applied clinically for human cancers. Preparation of adriamycin by fermentation of S. peuceticus var. caesius is disclosed in U.S. Pat. No. 3,590,028. Chemical conversion of daunomycin to adriamycin is taught in U.S. Pat. No. 3,803,124. Daunomycin (produced by fermentation of S. peuticus in U.K. 1,003,383) may be the same as Rhone-Poulenc's 13,057 R.P. (formerly rubidomycin and now daunoribicin: see U.K. Pat. Nos. 985,598, 1,188,262 and 1,241,750 and U.S. Pat. No. 3,616,242) and is probably identical to Ciba's danubomycin disclosed in U.S. Pat. No. 3,092,550 and U.K. Pat. No. 901,830. See also U.S. Pat. No. 3,686,163 on dihydrodaunomycin. Cinerubin A and Cinerubin B, glycosides having .epsilon.-pyrromycinone, are disclosed in U.K. Pat. No. 846,130 [see also U.S. Pat. No. 3,864,480 and Keller-Schierlein, et. al., Antimicrobial Agents and Chemotherapy, page 68 (1970) and Chemical Abstracts, 54, 1466i (1960)]. The anthracycline glycoside carminomycin described in J. Antibiotics 27:254-259 (1974), in West German Specification No. 2,362,707 and in J. Amer. Chem. Soc. 97 (20):5955-5956 (1975) has been reported to be active in several animal tumor systems. The antibiotic pyrromycin disclosed in Chem. Ber. 92:1904-1909 (1959) contains an aglycone .epsilon.-pyrromycinone and an amino sugar rhodosamine. For further illustrative and summary disclosures of anthracycline antibiotics see Index of Antibiotics from Actinomycetes, Hamao Umezawa, Editor-in-Chief, University Park Press, State College, Pennsylvania, U.S.A. (1967) as follows:
______________________________________ Antibiotic Page Number ______________________________________ Aklavin 111 Cinerubin A 220 Cinerubin B 221 Danubomycin 242 Daunomycin 243 Pyrromycin 524 Rhodomycin A, B 561 Rubidomycin 574 ______________________________________
The textbook Antibiotics, Vol. 1, Mechanism of Action, edited by David Gottlieb and Paul D. Shaw, Springer-Verlag New York, Inc., N.Y., N.Y. (1967) at pages 190-210 contains a review by A. DiMarco entitled Daunomycin and Related Antibiotics. Information Bulletin, No. 10, International Center of Information of Antibiotics, in collaboration with WHO, December 1972, Belgium, reviews anthracyclines and their derivatives.